This project is focused on the identification and characterization of a yeast transcriptional coactivator, the ADA/GCN5 complex. Five subunits of this complex were identified in the prior granting period by a novel genetic screen. One of the subunits, GCN5, has histone acetyl transferase activity, suggesting a biochemical mechanism of action of this coactivator. In the next period the research will purify the coactivator complex to homogeneity and study its biochemical properties in detail. This will reveal the role of each individual subunit in the complex and provide mechanistic insight into coactivator function. Also, genetic screens will get at the target of this complex in the general transcriptional machinery and detail the architecture within the complex. Also, the biochemical function of the C-terminal domain of GCN5 will be investigated. This region, termed the bromo-domain, is found in many diverse kinds of coactivators and its mechanism of action will prove central to transcriptional activation. Finally, a possible link between this coactivator and TBP will be investigated genetically and biochemically.